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Yushuf Sharker

Publications and source records attributed to Yushuf Sharker.

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Pairwise accelerated failure time regression models for infectious disease transmission in close-contact groups with external sources of infection

Many important questions in infectious disease epidemiology involve the effects of covariates (e.g., age or vaccination status) on infectiousness and susceptibility, which can be measured in studies of transmission in households or other close-contact groups. Because the transmission of disease produces dependent outcomes, these questions are difficult or impossible to address using standard regression models from biostatistics. Pairwise survival analysis handles dependent outcomes by calculating likelihoods in terms of contact interval distributions in ordered pairs of individuals. The contact interval in the ordered pair ij is the time from the onset of infectiousness in i to infectious contact from i to j, where an infectious contact is sufficient to infect j if they are susceptible. Here, we introduce a pairwise accelerated failure time regression model for infectious disease transmission that allows the rate parameter of the contact interval distribution to depend on infectiousness covariates for i, susceptibility covariates for j, and pairwise covariates. This model can simultaneously handle internal infections (caused by transmission between individuals under observation) and external infections (caused by environmental or community sources of infection). In a simulation study, we show that these models produce valid point and interval estimates of parameters governing the contact interval distributions. We also explore the role of epidemiologic study design and the consequences of model misspecification. We use this regression model to analyze household data from Los Angeles County during the 2009 influenza A (H1N1) pandemic, where we find that the ability to account for external sources of infection is critical to estimating the effect of antiviral prophylaxis.

stat.AP

Estimating and interpreting secondary attack risk: Binomial considered harmful

The household secondary attack risk (SAR), often called the secondary attack rate or secondary infection risk, is the probability of infectious contact from an infectious household member A to a given household member B, where we define infectious contact to be a contact sufficient to infect B if he or she is susceptible. Estimation of the SAR is an important part of understanding and controlling the transmission of infectious diseases. In practice, it is most often estimated using binomial models such as logistic regression, which implicitly attribute all secondary infections in a household to the primary case. In the simplest case, the number of secondary infections in a household with m susceptibles and a single primary case is modeled as a binomial(m, p) random variable where p is the SAR. Although it has long been understood that transmission within households is not binomial, it is thought that multiple generations of transmission can be safely neglected when p is small. We use probability generating functions and simulations to show that this is a mistake. The proportion of susceptible household members infected can be substantially larger than the SAR even when p is small. As a result, binomial estimates of the SAR are biased upward and their confidence intervals have poor coverage probabilities even if adjusted for clustering. Accurate point and interval estimates of the SAR can be obtained using longitudinal chain binomial models or pairwise survival analysis, which account for multiple generations of transmission within households, the ongoing risk of infection from outside the household, and incomplete follow-up. We illustrate the practical implications of these results in an analysis of household surveillance data collected by the Los Angeles County Department of Public Health during the 2009 influenza A (H1N1) pandemic.

q-bio.QM